Nitric oxide‐induced cytotoxicity attenuation by thiopentone sodium but not pentobarbitone sodium in primary brain cultures

Abstract

1. We describe the effects of barbiturates on the neurotoxicity induced by nitric oxide (NO) on foetal rat cultured cortical and hippocampal neurones. Cessation of cerebral blood flow leads to an initiation of a neurotoxic cascade including NO and peroxynitrite. Barbiturates are often used to protect neurones against cerebrovascular disorders clinically. However, its neuroprotective mechanism remains unclear. 2. In the present experiment, we established a new in vitro model of brain injury mediated by NO with an NO-donor, 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC-5) on grid tissue culture wells. We also investigated the mechanisms of protection of CNS neurones from NO-induced neurotoxicity by thiopentone sodium, which contains a sulphydryl group (SH-) in the medium, and pentobarbitone sodium, which does not contain SH-. 3. Primary cultures of cortical and hippocampal neurones (prepared from 16-day gestational rat foetuses) were used after 13-14 days in culture. The cells were exposed to NOC-5 at the various concentrations for 24 h in the culture to evaluate a dose-dependent effect of NOC-5. 4. To evaluate the role of the barbiturates, neurones were exposed to 4, 40 and 400 microM of thiopentone sodium or pentobarbitone sodium with or without 30 microM NOC-5. In addition, superoxide dismutase (SOD) at 1000 u ml(-1) and 30 microM NOC-5 were co-administered for 24 h to evaluate the role of SOD. 5. Exposure to NOC-5 induced neural cell death in a dose-dependent manner in both cortical and hippocampal cultured neurones. Approximately 90% of the cultured neurones were killed by 100 microM NOC-5. 6. This NOC-5-induced neurotoxicity was significantly attenuated by high concentrations of thiopentone sodium (40 and 400 microM) as well as SOD, but not by pentobarbitone sodium. The survival rates of the cortical neurones and hippocampal neurones that were exposed to 30 microM NOC-5 were 11.2+/-4.2% and 37.2+/-3.0%, respectively, and in the presence of 400 microM thiopentone sodium, the survival rate increased to 65.3+/-3.5% in the cortical neurones and 74.6+/-2.2% in the hippocampal neurones. 7. These findings demonstrate that thiopentone sodium, which acts as a free radical scavenger, protects the CNS neurones against NO-mediated cytotoxicity in vitro. In conclusion, thiopentone sodium is one of the best of the currently available pharmacological agents for protection of neurones against intraoperative cerebral ischaemia.

Thiopentone and methohexital, but not pentobarbitone, reduce early focal cerebral ischemic injury in rats

“…[25][26][27] During cerebral ischemia, neuronal nitric oxide synthase is activated 25 which can result in cytotoxicity by mechanisms which include free radical damage, inactivation of enzymes involved in mitochondrial respiration, and energy depletion subsequent to activation of poly-ADP ribose synthase. 28 In a neuronal cell culture model of nitric oxide induced cytotoxicity, Shibuta et al 29 assessed the effect of thiopentone and pentobarbitone on cell death. They observed that cell death was reduced by thiopentone but not pentobarbitone.…”

Propofol improves recovery from paraquat acute toxicity in vitro and in vivo

“…It may not be surprising that propofol and thiopental improved recovery from PQ acute toxicity in the cell culture study, because they are known to be free radical scavengers in vitro [13,14,15]. As thiopental was less potent than propofol in scavenging O 2 -, a larger concentration of thiopental was required to improve cell viability in the present study.…”

“…Ventilatory support is usually necessary for the treatment of PQ poisoning because of the consequences of the severe lung injury. Of the hypnotics and sedatives used in the management of mechanical ventilation, propofol and thiopental are recognized as having a free radical scavenging activity [13,14,15]. Because of this property, propofol is proposed to be useful for patients in intensive care units with multiorgan failure or acute respiratory distress syndrome [16].…”

Initial Observations of Combination Barbiturate Coma and Decompressive Craniectomy for the Management of Severe Pediatric Traumatic Brain Injury

“…Decompressive craniectomy has also been shown to decrease ICP as well as improve morbidity and mortality in TBI patients [1,10]. In the adult and pediatric populations, barbiturate coma and craniectomy are currently being used as a second tier means for controlling intracranial hypertension [4,7,10,11,12]. However, the combination of barbiturate coma and craniectomy for pediatric TBI, specifically in the severely injured population (GCS <5), has been limited to few studies.…”